4-[2-(4-methylpiperazin-1-yl)ethoxy]aniline

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound is prepared as described in Example 160A but using 4-[2-(4-methyl-piperazin-1-yl)-ethoxy]-phenylamine (500 mg, 2.13 mmol, 1 eq.), (6-chloro-pyrimidin-4-yl)-ethyl-amine and stirring the reaction mixture at 150° C. for 20 h. Purification of the crude product by silica gel column chromatography (DCM/MeOH+1% NH3aq, 9:1) followed by trituration in diethyl ether affords 250 mg of the title compound as a white solid: ESI-MS: 343.2 [MH]+; tR=1.00 min (gradient J); TLC: Rf=0.23 (DCM/MeOH+1% NH3aq, 9:1). The title compound is prepared Purification of the crude product by silica gel column chromatography (DCM/MeOH+1% NH3aq, 9:1)

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound is prepared as described in Example 160A but using 4-[2-(4-methyl-piperazin-1-yl)-ethoxy]-phenylamine (500 mg, 2.13 mmol, 1 eq.), (6-chloro-pyrimidin-4-yl)-ethyl-amine and stirring the reaction mixture at 150° C. for 20 h. Purification of the crude product by silica gel column chromatography (DCM/MeOH+1% NH3aq, 9:1) followed by trituration in diethyl ether affords 250 mg of the title compound as a white solid: ESI-MS: 343.2 [MH]+; tR=1.00 min (gradient J); TLC: Rf=0.23 (DCM/MeOH+1% NH3aq, 9:1). The title compound is prepared Purification of the crude product by silica gel column chromatography (DCM/MeOH+1% NH3aq, 9:1)

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound is prepared as described in Example 152A but using 4-[2-(4-methyl-piperazin-1-yl)-ethoxy]-phenylamine (300 mg, 1.28 mmol, 1 eq.), 6-chloro-pyrimidin-4-ylamine, water (0.5 ml), and stirring the reaction mixture for 2 h at 150° C. The crude product is purified by trituration in diethyl ether to afford the title compound as a white solid. ESI-MS: 329.1 [MH]+; tR=0.98 min (purity: 100%, gradient J). The title compound is prepared The crude product is purified by trituration in diethyl ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a microwave vial, 2-Methanesulfinyl-7-pyridin-3-yl-pyrrolo[2,1-f][1,2,4]triazine (0.104 g, 0.000404 mol), 4-[2-(4-Methyl-piperazin-1-yl)-ethoxy]-phenylamine (0.209 g, 0.000888 mol), 1-Methoxy-2-propanol (0.971 mL, 0.00993 mol) and N,N-Diisopropylethylamine (0.155 mL, 0.000888 mol) were added. The reaction was microwaved on 300 watts, 170° C. for 50 minutes. The solvent was removed under vacuum. The desired product was isolated via ISCO column chromatography with DCM and methanol as eluant (0 to 12% methanol). The collected fractions afforded {4-[2-(4-Methyl-piperazin-1-yl)-ethoxy]-phenyl}-(7-pyridin-3-yl-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-amine as a yellow solid (28 mg, 16%). MP 107-110° C. LCMS (E/I+) 430.8 (M+H). NMR 1H (DSMO-d6)-9.42 (d, 1H, J=2.00), 9.39 (s, 1H), 9.04 (s, 1H), 8.66 (d, 1H, J=7.76 Hz), 8.61 (d, 1H, J=6.56 Hz), 7.60-7.70 (m, 3H), 7.32 (d, 1H, J=4.77 Hz), 6.98 (d, 1H, J=4.76 Hz), 6.95 (d, 2H, J=9.00 Hz), 4.16 (t, 2H, J=5.26 Hz), 2.40-3.50 (m, 13H). The reaction was microwaved on 300 watts, 170° C. for 50 minutes The solvent was removed under vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The titled compound was prepared in an analogous fashion to Example 47 replacing 6-Morpholin-4-yl-pyridin-3-ylamine with 4-[2-(4-Methyl-piperazin-1-yl)-ethoxy]-phenylamine to [7-(2-Methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-{4-[2-(4-methyl-piperazin-1-yl)-ethoxy]-phenyl}-amine; compound with trifluoro-acetic acid as a yellow powder. LCMS (E/I+) 459.9 (M+H). NMR 1H (DSMO-d6)-9.27 (s, 1H), 8.93 (s, 1H7.81 (dd, 1H, Jj=1.40, 6.17 Hz), 7.65 (d, 2H, J=9.00 Hz), 7.45 (t, 1H, J=9.72 Hz), 7.21 (d, 1H, J=8.32 Hz), 7.12 (t, 1H, J=7.49 Hz), 6.94 (d, 1H, J=4.61 hz), 6.91 (d, 1H, J=4.64), 6.84 (d, 2H, J=9.00 Hz), 4.19 (t, 2H, J=4.72 Hz), 3.78 (s, 3H), 2.90-3.70 (bm, 10), 2.84 (s, 3H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a Round bottom flask, 1-Methyl-4-[2-(4-nitro-phenoxy)-ethyl]-piperazine (3.89 g, 0.0147 mol), 10% Pd/C (10:90, Palladium:carbon black, 1.6 g, 0.0015 mol), and Ethanol (100 mL, 2 mol) were added. The mixture was evacuated under house vacuum and charged with a hydrogen balloon (3×). The reaction was stirred at room temperature under an atmosphere of Hydrogen via a balloon. The solid was filtered. The solvent was removed under vacuum. The desired product was purified via ISCO column chromatography with DCM and methanol as eluant (0 to 10%). The collected fractions afforded 4-[2-(4-Methyl-piperazin-1-yl)-ethoxy]-phenylamine as a red solid (2.35 g, 68%). NMR 1H (DSMO-d6-6.63 (dd, 2H, JJ=1.92, 4.72 Hz), 6.48 (dd, 2H, JJ=1.96, 4.72 Hz), 4.52 (bs, 2H), 3.89 (t, 2H, J=5.92 Hz), 2.59 (t, 2H, J=5.92 Hz), 2.44 (bs, 4H), 2.29 (bs, 4H), 2.13 (s, 3H) The mixture was evacuated under house vacuum charged with a hydrogen balloon (3×) The solid was filtered The solvent was removed under vacuum The desired product was purified via ISCO column chromatography with DCM and methanol as eluant (0 to 10%)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,6-difluorobenzamide and 4-{[2-(4-methyl-1-piperazinyl)ethyl]oxy}aniline in a manner analogous to Example 64. 1H NMR (400 MHz, DMSO-d6) δ 2.11 (s, 3H), 2.20-2.35 (m, 4H), 2.62 (t, 2H, J=5.8 Hz), 3.00-3.60 (m, 4H overlapping with H2O), 3.98 (t, 2H, J=5.8 Hz), 6.47 (d, 1H, J=5.1 Hz), 6.80 (d, 2H, J=9.0 Hz), 7.08 (t, 1H, J=6.9 Hz), 7.22 (t, 2H, J=8.0 Hz), 7.31 (d, 1H, J=7.5 Hz), 7.41-7.60 (m, 5H), 7.80 (d, 1H, J=8.1 Hz), 7.97 (s, 1H), 8.16-8.21 (m, 1H), 8.39 (bd, 1H, J=7.4 Hz), 8.81 (d, 1H, J=6.8 Hz), 9.31 (s, 1H), 10.91 (s, 1H); ESIMS (M+H)+=661.

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound is prepared as described in Example 152A but using 4-[2-(4-methyl-piperazin-1-yl)-ethoxy]-phenylamine (300 mg, 1.28 mmol, 1 eq.), 6-chloro-pyrimidin-4-ylamine, water (0.5 ml), and stirring the reaction mixture for 2 h at 150° C. The crude product is purified by trituration in diethyl ether to afford the title compound as a white solid. ESI-MS: 329.1 [MH]+; tR=0.98 min (purity: 100%, gradient J). The title compound is prepared The crude product is purified by trituration in diethyl ether

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound is prepared as described in Example 160A but using 4-[2-(4-methyl-piperazin-1-yl)-ethoxy]-phenylamine (500 mg, 2.13 mmol, 1 eq.), (6-chloro-pyrimidin-4-yl)-ethyl-amine and stirring the reaction mixture at 150° C. for 20 h. Purification of the crude product by silica gel column chromatography (DCM/MeOH+1% NH3aq, 9:1) followed by trituration in diethyl ether affords 250 mg of the title compound as a white solid: ESI-MS: 343.2 [MH]+; tR=1.00 min (gradient J); TLC: Rf=0.23 (DCM/MeOH+1% NH3aq, 9:1). The title compound is prepared Purification of the crude product by silica gel column chromatography (DCM/MeOH+1% NH3aq, 9:1)